Most cell reactions occur in an aqueous medium. Although the general importance of solvent participation in biochemical processes is recognized, the ways in which solvent can enter into a reaction have not been described adequately. Part of the difficulty in doing this is the lack of understanding of macromolecule-solvent interactions. Various approaches to this problem are considered here. First, heat capacity measurements offer a means of studying protein-solvent interactions over the full range of system composition. Measurements on a membrane protein and other cell components will be made to extend previous work on lysozyme and t-RNA. Second, the effect of hydration or motional properties of protein and t-RNA will be studied using hydrogen exchange and ESR probes. Third, the effect of hydration on enzymatic activity (e.g., urease) will be measured, extending previous work with lysozyme. Fourth, a sorption isotherm not previously applied to proteins will be tested.